This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To explore the possible utility of calcium and strontium stable isotope techniques in the assessment of bone mineral balance. Osteoporosis, characterized by low bone mass and disordered trabecular architecture with attendant skeletal fragility, is among the most common diseases of older people. Worldwide, osteoporosis affects 1 in 3 women and 1 in 4 men over 50 years of age. Additionally, the incidence of osteoporosis-related hip fracture is expected to double in the next 20yrs with increasing population size and life expectancy. Nutritional insufficiencies, genetic predisposition, decreased physical activity, "age-related" factors, and estrogen deficiency all likely contribute to the pathophysiology of postmenopausal and age-related osteoporosis. Skeletal turnover and bone loss rapidly increase following reduction of circulating estrogen levels resulting from menopause or ovariectomy, highlighting the critical role of estrogen in the genesis of osteoporosis in women. Biochemical markers of bone turnover are of marginal clinical value, are poorly suited to detect rapid alterations in bone mineral kinetics (critical components of skeletal response to endocrine change), and cannot be used to measure net bone mineral balance. To overcome these problems, we propose employing calcium (Ca) and strontium (Sr) stable isotope techniques that are well validated in geochemistry, but rarely applied in biomedicine. These techniques, which promise to provide data on bone mineral balance of unprecedented detail and precision, will be validated and applied to a unique animal model of hypoestrogenic bone mass maintenance. These novel, noninvasive techniques will prove invaluable to osteoporosis research and afford high promise for future research and clinical applications This research used Animal Services and Research Services.